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Medical Policy Bulletin

ADAMTS13, recombinant-krhn (Adzynma)
08.02.21

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY
PROPHYLACTIC TREATMENT​​

ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma)​, is considered medically necessary and, therefore, covered for the prophylactic treatment of congenital thrombotic thrombocytopenic purpura (Misspelled WordcTTP) in adult and pediatric individuals, when all of the following criteria are met, including dosing and frequency:

Initial Criteria
  • Diagnosis of Misspelled WordcTTP:
    • ADAMTS13 mutation is confirmed by molecular genetic testing with Misspelled Wordbiallelic mutations in the ADAMTS13 gene
    • ​The individual has an ADAMTS13 activity level of less than 10% at the time of diagnosis​
  • ADAMTS13, recombinant-Misspelled Wordkrhn​ (Misspelled WordAdzynma) is being prescribed for routine prophylactic treatment to prevent thrombotic thrombocytopenic purpura (TTP) events
  • Prescribed by or in consultation with a hematologist
  • Dosing and frequency for ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma)​:
    • 40 IU/kg body weight once every other week intravenously
    • The prophylaxis dosing frequency may be adjusted to 40 IU/kg body weight once weekly based on prior prophylactic dosing regimen or clinical response
Continuation Criteria
  • The individual has previously received routine prophylactic treatment with ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma)
  • Documentation of positive clinical response to ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma) therapy (e.g., reduction or maintenance of number of TTP events, increase in platelet count, decrease in lactate dehydrogenase [LDH] level)
  • Prescribed by or in consultation with a hematologist
TREATMENT

ADAMTS13, recombinant-Misspelled Wordkrhn
 (Misspelled WordAdzynma) is considered medically necessary and, therefore, covered for on demand treatment of an acute TTP event in adult and pediatric individuals, when all of the following criteria are met, including dosing and frequency:

  • Diagnosis of congenital thrombotic thrombocytopenic purpura (Misspelled WordcTTP):
    • ADAMTS13 mutation is confirmed by molecular genetic testing with Misspelled Wordbiallelic mutations in the ADAMTS13 gene
    • ​The individual has an ADAMTS13 activity level of less than 10% at the time of diagnosis​
  • ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma) is being prescribed for on demand treatment of an acute thrombotic thrombocytopenic purpura (TTP) event
  • Prescribed by or in consultation with a hematologist
  • Dosing and frequency for ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma)​: 
    • 40 IU/kg body weight on day one
    • 20 IU/kg body weight on day two
    • 15 IU/kg body weight on day three and beyond until two days after the acute event is resolved
EXPERIMENTAL/INVESTIGATIONAL

All other uses for ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma)​, are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this policy to ensure consistency with the most recently published recommendations for the use of ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma)​ outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the utilization management activities. The Company reserves the right to conduct postpayment review and audit procedures for any claims submitted for ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma)​.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.

When coverage of ADAMTS13, recombinant-Misspelled Wordkrhn (Misspelled WordAdzynma)​, is requested outside of the Dosing and Frequency Requirements listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.

Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, ADAMTS13, recombinant-krhn (Adzynma) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

ADAMTS13, recombinant-krhn (Adzynma) was approved by the FDA on November 09, 2023,​ for the prophylactic and on-demand treatment of adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).

PEDIATRIC USE

The safety and effectiveness have been established in the pediatric population​ for ADAMTS13, recombinant-krhn (Adzynma).

Description

DRUG INFORMATION

ADAMTS13, recombinant-krhn (Adzynma), is a human recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” (rADAMTS13) indicated for prophylactic or on-demand enzyme replacement therapy (ERT) in adult and pediatric individuals with congenital thrombotic thrombocytopenic purpura (cTTP)​.

CONGENITAL ADAMTS13 DEFICIENCY

Congenital thrombotic thrombocytopenic purpura (cTTP) is an autosomal recessive disorder caused by biallelic mutations on the ADAMTS13 gene. It is characterized by less than 10% ADAMTS13 enzyme activity and the accumulation of ultra-large von Willebrand factor (VWF). The buildup of ultra-large VWF multimers leads to uncontrolled platelet aggregation, platelet adhesion, and abnormal clotting in the small blood vessels. cTTP often causes seemingly mild and nonspecific symptoms such as lethargy, headache, loss of concentration, and abdominal discomfort.

ADAMTS13 deficiency is most commonly acquired due to anti-ADAMTS13 autoantibodies. It can also be inherited in the congenital form as a result of biallelic mutations in the ADAMTS13 gene. 
cTTP is a rare blood disorder characterized by blood clotting due to a deficiency in the enzyme ADAMTS13, affecting fewer than 1000 people in the United States. The most common presentation of cTTP includes thrombocytopenia, microangiopathic hemolytic anemia, headaches, and abdominal pain. The mortality of acute thrombotic thrombocytopenic purpura (TTP) events can reach 90% or higher if the disease is left untreated. Treatment has normally included prophylactic plasma-based therapy. 

The 2020 International Society on Thrombosis and Haemostasis (ISTH) good practice statements for the clinical care of individuals with TPP state that TTP should be considered in individuals presenting with thrombocytopenia and microangiopathic hemolytic anemia. cTTP should be suspected in individuals with any of the following presentations: severe neonatal hyperbilirubinemia, recurrent thrombocytopenia in a child or young adult, transient neurologic symptoms of stroke in a child or young adult, embolic stroke of undetermined source, or new-onset TTP and absence of an ADAMTS13 inhibitor. Once suspected, individuals​ should be tested for decreased ADAMTS13 enzyme activity, and if the enzymatic activity is less than 10% of normal without ADAMTS13 antibodies, genetic testing showing biallelic mutations in the ADAMTS13 gene will be confirmatory of cTPP.

PEER-REVIEWED LITERATURE

SUMMARY

The safety and effectiveness of ADAMTS13, recombinant-krhn​ (Adzynma) ​were demonstrated in a global study evaluating prophylactic and on-demand ERT with ADAMTS13, recombinant-krhn (Adzynma)​compared to plasma-based therapies in patients with cTTP. 

The efficacy of ADAMTS13, recombinant-krhn​ (Adzynma) in the prophylactic treatment of patients with cTTP was evaluated in 46 patients who were randomly assigned to receive 6 months of treatment with either ADAMTS13, recombinant-krhn​ (Adzynma) or plasma-based therapies (Period 1), then crossed over to the other treatment for 6 months (Period 2). The efficacy was demonstrated based on the incidence of TTP events, and TTP manifestations, as well as the incidence of the need for supplemental doses. 

The efficacy of on-demand ERT was evaluated based on the proportion of acute TTP events responding to ADAMTS13, recombinant-krhn​ (Adzynma) in both the prophylactic and the on-demand cohorts throughout the duration of the study. All acute and subacute TTP events resolved after treatment with either ADAMTS13, recombinant-krhn​ (Adzynma) or plasma-based therapies. 

The most common side effects associated with ADAMTS13, recombinant-krhn​ (Adzynma) include headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness, and vomiting. During the clinical studies, no adverse events, including allergic reactions, were observed during the administration of ADAMTS13, recombinant-krhn​ (Adzynma). Thirteen (one individual in Study 1 and twelve individuals in a long-term extension study) of 67 individuals treated prophylactically with ADAMTS13, recombinant-krhn​ (Adzynma) with confirmed cTTP tested positive for low-titer binding antibodies against ADAMTS13 with no observable clinical impact on the safety or efficacy of ADAMTS13, recombinant-krhn​ (Adzynma), and no increase in antibody titers over time. No cTTP individuals tested positive for neutralizing antibodies against ADAMTS13, recombinant-krhn​ (Adzynma)​.

The application was awarded a Rare Pediatric Disease Priority Review Voucher, and granted Priority Review, Fast Track and Orphan designations.

OFF-LABEL INDICATIONS

There may be additional indications contained in the policy section of this document due to evaluation of criteria highlighted in the company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.​

References

American Hospital Formulary Service–Drug Information (AHFS-DI). ADAMTS13, recombinant-krhn. [LexiComp Web site]. 03/11/2024. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed May 14, 2024.

Asmis LM, Serra A, Krafft A, et al. Recombinant ADAMTS13 for Hereditary Thrombotic Thrombocytopenic Purpura. N Engl J Med 2022; 387:2356-2361.

Centers for Medicare & Medicaid Services' (CMS). Guidance for Prior Authorization and Step Therapy for Part B Drugs in Medicare Advantage. 08/07/2018. Available at: https://www.cms.gov/Medicare/Health-Plans/HealthPlansGenInfo/Downloads/MA_Step_Therapy_HPMS_Memo_8_7_2018.pdf.

Clinicaltrials.gov. A study of BAX 930 in children, teenagers, and adults born with thrombotic thrombocytopenic purpura (TTP) (NCT03393975). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT03393975. Accessed on May 13, 2024​.

Clinicaltrials.gov. A study of TAK-755 in participants with congenital thrombotic thrombocytopenic purpura (NCT04683003). Available at: https://classic.clinicaltrials.gov/ct2/show/study/NCT04683003. Accessed on May 13, 2024.

Elsevier’s Clinical Pharmacology CompendiumADAMTS13, recombinant-krhn (Adzynma)[Clinical Key Web site]. 04/17/24. Available at: https://www.clinicalkey.com/pharmacology/monograph/3533?n=Soliris [via subscription only]. Accessed May 14, 2024.

Lexi-Drugs Compendium. ADAMTS13, recombinant-krhn​ (Adzynma). [Lexicomp Online Web site]. 04/25/2024. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed May 14, 2024.

Scully M,  Knöbl P, Kentouche K, et. al. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood. 2017;30(19): 2055-2063. 

Sukumar S, Lämmle B, Cataland SR. Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management. J Clin Med. 2021;10(3):536. 

Takeda Pharmaceuticals, Inc. ADAMTS13, recombinant-krhn (Adzynma)​​ labeling. Available at: content.takeda.com/?contenttype=PI&product=ADZ&language=ENG&country=USA&documentnumber=1. 11/2023. Accessed May 14, 2024.

Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. ADAMTS13, recombinant-krhn​​. [Micromedex Web site]. 04/12/24. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed May 14, 2024.

Coding

CPT Procedure Code Number(s)
N/A

ICD - 10 Procedure Code Number(s)
N/A

ICD - 10 Diagnosis Code Number(s)
D69.42 Congenital and hereditary thrombocytopenia purpura

HCPCS Level II Code Number(s)
J7171 Injection, adamts13, recombinant-krhn, 10 iu​

Revenue Code Number(s)
N/A

Policy History

Revisions From 08.02.21:
07/15/2024This v​ersion of the policy will become effective 07/15/2024​.

This new policy has been issued to communicate the Company’s coverage position and criteria for ADAMTS13, recombinant-krhn (Adzynma)​.


07/15/2024
07/15/2024
N/A
08.02.21
Medical Policy Bulletin
Commercial
No